1. Field of the Invention
The present invention relates generally to a method of manufacturing microfluidic chips for handling fluid samples on a microfluidic level, and, more specifically, to a method of manufacturing microfluidic chips with coating to reduce fluid diffusion and microfluidic chips with a coating to reduce fluid diffusion. The manufactured microfluidic chips can be used to perform real-time analysis, for example, polymerase chain reaction (PCR) analysis.
2. Discussion of the Related Art
Microfluidics can be used in medicine or cell biology researches and refers to the technology that relates to the flow of liquid in channels of micrometer size. At least one dimension of the channel is of the order of a micrometer or tens of micrometers to be considered as microfluidics. In particular, microfluidic devices are useful for manipulating or analyzing micro-sized fluid samples on microfluidic chips, with the fluid samples typically in extremely small volumes down to less than pico liters.
When manipulating or analyzing fluid samples, fluids are pumped onto the micro-channel of microfluidic chips in doses or are continuously flowed onto the micro-channel of microfluidic chips. If the fluid sample is pumped in doses, the fluid sample stays in the micro-channel of the microfluidic chip until the fluid sample is suctioned out from the micro-channel. The fluid sample can be manipulated or analyzed while being held in the micro-channel.
Alternatively, for continuous flow analysis, the fluid is pumped continuously into the micro-channel. Due to the continuous fluid pumping, the fluid sample instead flows and travels through the micro-channel and exits the micro-channel when reaches the outlet of the micro-channel. The fluid sample can be manipulated or analyzed while flowing through the micro-channel, and one can perform a biochemical reaction examination on the continuously flowing fluid sample, including treating and manipulating processes of the fluid.
Presently, microfluidic chips have micro-channels molded in PolyDiMethyiSiloxane (“PDMS”). The micro-channels then are sealed when the PDMS block is bonded to a glass slide.
FIGS. 1A-1D are perspective views of manufacturing a microfluidic chip mold according to the related art. The manufacturing of a microfluidic chip according to the related art takes a channel design and duplicates the channel design onto a photomask 10. As shown in FIG. 1A, a photoresist 22 is deposited onto a semiconductor wafer 20. As shown in FIG. 1B, the photomask 10 that reflects the channel design 12 is placed over the wafer 20, and the wafer 20 with the mask 10 undergoes UV exposition to cure the photoresist 22. Then, as shown in FIG. 1C, the wafer 20 with the cured photoresist 22′ is developed. The ‘negative’ image of a channel according to the channel design is etched away from the semiconductor wafer 20. As shown in FIG. 1D, after all residual photoresist are removed, the resulting wafer becomes a mold 20 that provides the channel according to the channel design 12′.
FIG. 2 are perspective views of the steps of manufacturing a microfluidic chip according to the related art. As shown in FIG. 2, PDMS in liquid form 30 is poured onto the mold 20′. Liquid PDMS 30 may be mixed with crosslinking agent. The mold 20′ with liquid PDMS 30 is then placed into a furnace to harden PDMS 30. As PDMS is hardened, the hardened PDMS block 30′ duplicates the micro-channel 12″ according to the channel design. The PDMS block 30′ then may be separated from the mold 20′. To allow injection of fluid into the micro-channel 12″ (which will subsequently be sealed), inlet or outlet is then made in the PDMS block 30′ by drilling into the PDMS block 30′ using a needle. Then, the face of the PDMS block 30′ with micro-channels and a glass slide 32 are treated with plasma. Due to the plasma treatment, the PDMS block 30 and the glass slide 32 can bond with one another and close the chip.
The microfluidic chip according to the related art has a micro-channel in the PDMS block. PDMS belongs to a group of polymeric organosilicon compounds that are commonly referred to as silicone, and can be deposited onto the master mold in liquid form and subsequently hardened.
However, PDMS is inherently porous and due to its polymer structure, PDMS is highly permeable. Thus, diffusion of fluid sample through PDMS has been observed. Such diffusion of fluid sample does not impact a microfluidic system that pumps fluid samples in doses as significantly as a continuous flow microfluidic system. In particular, when a continuous flow microfluidic system monitors treating and manipulating of the flowing fluid in real-time analysis applications, diffusion or unaccounted loss of fluid sample can significantly impact the real-time analysis. Thus, there exists a need for reducing diffusion or loss of fluid sample in micro-channel of a microfluidic chip.